Nonhuman primates represent the only natural and experimental host for simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV). In particular, macaques are being used as the primary model for AIDS-related studies. This vaccine approach is a new one and offers direct antigen presentation. The results of this project may lead to novel vaccine strategies for HIV and other pathogens. Macaques will be immunized with antigen-presenting cells (APC), purified from autologous peripheral blood mononuclear cells (PBMC), pulsed with SIV antigens or transfected with DNA expression vectors for SIV antigens in vitro, then reinfused intravenously. All 14 macaques will be immunized with Tetanus Toxoid twice at four-week intervals prior to APC immunization to establish immune responses to a particulate antigen. One group of 5 macaques will receive APC pulsed with Gag-Pol and Env particles of SIVMne, a second group of 5 macaques will receive APC transfected with Env , Gag-Pol-Env, and Nef vectors of SIVMne. A third group of 4 macaques will be infused with APC transfected with vector alone. All 14 macaques recently received the first immunization of APC. FUNDING NIH grant RR00166 and NIAID grant AI42666.